Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons

Brain Sciences

Tian Zhou¹  Jiang Chen²  Zi-Yang Liu²  Bin Luo²  Er-Kang Fei²  Wen-Bing Chen² 

[1] School of Basic Medical Sciences, Nanchang University, Nanchang 330031, China;School of Life Sciences, Nanchang University, Nanchang 330031, China;

关键词: metformin;    glutamate release;    neuronal excitability;    hippocampal;    pyramidal neurons;   

DOI  :  10.3390/brainsci10100706

来源: DOAJ

【 摘 要 】

Metformin (Met) is a first-line drug for type 2 diabetes mellitus (T2DM). Numerous studies have shown that Met exerts beneficial effects on a variety of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). However, it is still largely unclear how Met acts on neurons. Here, by treating acute hippocampal slices with Met (1 μM and 10 μM) and recording synaptic transmission as well as neuronal excitability of CA1 pyramidal neurons, we found that Met treatments significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), but not amplitude. Neither frequency nor amplitude of miniature inhibitory postsynaptic currents (mIPSCs) were changed with Met treatments. Analysis of paired-pulse ratios (PPR) demonstrates that enhanced presynaptic glutamate release from terminals innervating CA1 hippocampal pyramidal neurons, while excitability of CA1 pyramidal neurons was not altered. Our results suggest that Met preferentially increases glutamatergic rather than GABAergic transmission in hippocampal CA1, providing a new insight on how Met acts on neurons.

【 授权许可】

Unknown